medical research/news item: (UK) Study finds EPB41L3 'protector gene' inactivated in 65% of ovarian cancers

Note: in research

"A new gene that normally protects againstovarian cancer is switched-off in two-thirds of cases of the disease, reveals a study published in the journal Neoplasia today.
This 'protector gene', known as EPB41L3, is inactivated in 65 per cent of ovarian cancers. And reactivating the gene halted tumour growth and triggered large numbers of the cancer cells to commit suicide. The research, co-funded by Cancer Research UK and gynaecological cancer research charity
The Eve Appeal, raises the prospect for developing therapies that mimic or restore the function of the gene to kill ovarian cancer cells in a targeted way...."

press release: Clarient Receives Patents for Taxane Biomarker - TLE3 (gene)

Note: Transducin-like enhancer protein 3 is a protein that in humans is encoded by the TLE3 gene

"Clarient, Inc., a premier technology and services resource for pathologists, oncologists and the pharmaceutical industry, today announced that the United Kingdom Patent Office has granted a U.K. patent on the Company's TLE3 biomarker, a marker which may be used to predict which cancer patients will respond favorably to taxane therapy. In addition, the Company has received a Notice of Allowance from the United States Patent and Trademark Office (USPTO) for a U.S. patent on the TLE3 biomarker. Other patents for the TLE3 biomarker are pending in the U.S., Canada, Japan, China, India and elsewhere in Europe.

The U.S. patent will cover uses of the TLE3 biomarker in breast cancer. The U.K. patent covers uses of TLE3 in breast, lung and ovarian cancers.
Taxanes are important cancer therapeutics which, in combination with other cancer therapies, can markedly improve a patient's response rate to therapy. However, taxanes also carry with them a significant incidence of severe side effects, making it important to identify which patients will most likely benefit from the therapy.

"Given the frequent prescription of taxanes in the U.S., the U.K. and elsewhere in Europe and the world, we are very excited about the granting of these patents and the protection they provide our taxane sensitivity marker," said Clarient Vice Chairman and CEO Ron Andrews."

Cancer genetics and reproduction

Abstract

Cancers of the reproductive organs (i.e., ovaries, uterus and testes), like other cancers, occur as a result of a multi-stage interaction of genetic and environmental factors. A small proportion of cancers of the reproductive organs occur as part of a recognised cancer syndrome, as a result of inheritance of mutations in highly penetrant cancer susceptibility genes (e.g., BRCA1, BRCA2, MLH1 or MSH2). Recognition of individuals and families with inherited cancer predisposition syndromes and individuals at high risk due to familial cancer clustering is fundamentally important for the management and treatment of the current cancer and for future prevention of further cancers for the individual and their extended family

Comprehensive Analysis of Missense Variations in the BRCT Domain of BRCA 1 by Structural and Functional Assays

Comprehensive Analysis of Missense Variations in the BRCT Domain of BRCA1 by Structural and Functional Assays.

Lee MS, Green R, Marsillac SM, Coquelle N, Williams RS, Yeung T, Foo D, Hau DD, Hui B, Monteiro AN, Glover JN.

Authors' Affiliations: Department of Biochemistry, School of Systems Molecular Medicine, University of Alberta, Edmonton, Alberta, Canada; National Institute of Environmental Health Sciences, Durham, North Carolina; Risk Assessment, Detection, and Intervention Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida; and Molecular Biology Program, Institute of Biophysics Carlos Chagas Fo., Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
Abstract

Genetic screening of the breast and ovarian cancer susceptibility gene BRCA1 has uncovered a large number of variants of uncertain clinical significance. Here, we use biochemical and cell-based transcriptional assays to assess the structural and functional defects associated with a large set of 117 distinct BRCA1 missense variants within the essential BRCT domain of the BRCA1 protein that have been documented in individuals with a family history of breast or ovarian cancer....... Through a correlation of the assay results with available family history and clinical data, we define limits to predict the disease risk associated with each variant. Forty-two of the variants show little effect on function and are likely to represent variants with little or no clinical significance; 50 display a clear functional effect and are likely to represent pathogenic variants; and the remaining 25 variants display intermediate activities. The excellent agreement between the structure/function effects of these mutations and available clinical data supports the notion that functional and structure information can be useful in the development of models to assess cancer risk.